Hypospadias, trouble du déterminisme du sexe

Abstract

Introduction: Hypospadias, a complex urogenital malformation, raises significant concerns in pediatric urology due to its varied clinical implications. This thesis focused on a comprehensive approach, including an epidemiological study and a molecular analysis, aimed at elucidating the risk factors and genetic bases of this condition within the Algerian population. Methods: A retrospective epidemiological study was conducted on cases operated on between 2007 and 2022 in eastern Algeria. Molecular analysis was performed on 110 patients and 125 controls using PCR and PCR/RFLP techniques to examine genetic variations. Results: The retrospective epidemiological study revealed a stable prevalence of hypospadias, with the majority of cases managed between 0 and 5 years. Duckett's classification highlighted a predominance of cases with an anterior urethral meatus position, while severity assessment showed that approximately a quarter of the cases were severe, often associated with complex genital anomalies such as micropenis and testicular ectopia. Risk factor analysis highlighted significant associations with advanced maternal age, diabetes, and gestational hypertension, as well as consanguinity. Neonatal parameters like low birth weight and prematurity were also strongly correlated with this malformation. The molecular analysis enhanced our understanding of the genetic bases of hypospadias in the Algerian population. Y chromosome microdeletions were absent in all studied patients. Conversely, significant associations were found between the C677T variant of the MTHFR gene and the risk of hypospadias, suggesting that hyperhomocysteinemia related to this variant might disrupt folate metabolism and affect embryonic genital development. In contrast, analysis of the A>G variant of the DICER1 gene did not reveal a correlation with hypospadias, although the G allele is rare in this population. Conclusion: This thesis makes significant contributions to the integrated understanding of epidemiological and genetic factors of hypospadias in Algeria. The results highlight the importance of a multidisciplinary approach for clinical management and future research, aiming to improve early screening, surgical management, and preventive strategies for this complex medical condition.